E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension |
Hipertensión arterial pulmonar |
|
E.1.1.1 | Medical condition in easily understood language |
Disease in which blood vessels (arteries) in the lungs are damaged. This inhibits blood flow and pressure in the lung arteries rises and eventually heart failure develops |
Enfermedad en la que las arterias en los pulmones están dañados. Esto inhibe el flujo sanguíneo y la presión en las arterias pulmonares aumenta y, finalmente, se desarrolla insuficiencia cardíaca. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of LTP001 in participants with pulmonary arterial hypertension |
Evaluar la eficacia de LTP001 en pacientes con hipertensión arterial pulmonar |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of LTP001 on other efficacy measures, Patient reported outcomes and biomarkers - To assess the safety and tolerability of LTP001 in participants with PAH - To investigate the pharmacokinetics (PK) of LTP001 |
• Evaluar el efecto de LTP001 en otras medidas de eficacia, resultados comunicados por el paciente y biomarcadores. • Evaluar la seguridad y la tolerabilidad de LTP001. • Investigar la farmacocinética (PK) de LTP001. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- History of PAH belonging to one of the following subgroups of the Clinical Classification Group 1 (WHO): --> participants with idiopathic pulmonary arterial hypertension (IPAH) --> Hereditary pulmonary arterial hypertension --> Congenital heart disease (surgically repaired at least 12 months prior to screening) --> drug or toxin induced (for example, anorexigen or methamphetamine use) - Resting mean pulmonary arterial pressure > 25 mmHg; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure < 15 mmHg as determined by right heart catheterization - Pulmonary Vascular Resistance > 6 Wood unites (480 dynes s/cm5), as determined by right heart catheterization - WHO Functional Class II-III - 6MWD must be between 150 and 550 m (inclusive). - Standard of care therapy which is stable at least 6 weeks prior to RHC and 6MWT assessment
Other protocol-defined criteria may apply. |
- Antecedentes de HAP de uno de los siguientes subgrupos del grupo 1 de la clasificación clínica de la HAP de la Organización Mundial de la Salud (OMS): -- Participantes con hipertensión pulmonar arterial primaria idiopática (HPAPI). -- Hipertensión arterial pulmonar hereditaria. -- Enfermedad cardíaca congénita (reparada quirúrgicamente al menos 12 meses antes de la selección). -- Inducida por fármacos o toxinas (por ejemplo, uso de anorexígenos o metanfetaminas). - Presión arterial pulmonar media (PAPm) en reposo >25 mmHg; presión de enclavamiento capilar pulmonar (PECP) o presión telediastólica ventricular izquierda (PTDVI) <15 mmHg determinadas por cateterismo cardíaco derecho (CCD) - Resistencia vascular pulmonar (RVP) >6 unidades Wood (480 dinas s/cm5), determinada por cateterismo cardíaco derecho. - Clase funcional II-III de la OMS. - La 6MWD debe estar entre 150 y 550 m (inclusive). - Tratamiento estándar estable al menos 6 semanas antes del CCD y prueba de aptitud de 6MWT
Para mas criterios ver protocolo |
|
E.4 | Principal exclusion criteria |
- Participants with pulmonary hypertension (PH) in the Clinical Classification Groups 2-5 (WHO), and any PAH Group 1 subgroups that were not covered by the inclusion criteria. - Participants with a history of left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease compromising left ventricular function and/or pulmonary venous hypertension or symptomatic coronary disease - Participants with obstructive lung disease defined as: FEV1/FVC < 60% and FEV1 < 60% of predicted value after bronchodilator administration as well as participants with moderate or severe restrictive lung disease: Total Lung Capacity < 70% of predicted value. - Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity and execution of study procedures such as 6MWT .
Other protocol-defined criteria may apply. |
• Participantes con hipertensión pulmonar (HP) de los grupos 2-5 de la clasificación clínica de la OMS y de cualquier subgrupo del grupo 1 de la HAP no incluido en el criterio de inclusión. • Participantes con antecedentes de enfermedad cardíaca del lado izquierdo, insuficiencia cardíaca crónica del lado izquierdo, enfermedad valvular congénita o adquirida que afecte a la función ventricular izquierda, hipertensión venosa pulmonar o enfermedad coronaria sintomática • Participantes con enfermedad pulmonar obstructiva definida como: FEV1/FVC <60 % y FEV1 <60 % del valor teórico después de la administración de broncodilatadores, así como participantes con enfermedad pulmonar restrictiva moderada o grave: Capacidad pulmonar total <70 % del valor teórico. • Deterioro agudo o crónico (excluyendo la disnea) que limite la capacidad de cumplir los requisitos del estudio, incluyendo la interferencia con la actividad física y la ejecución de los procedimientos del estudio como la 6MWT.
Para más criterios ver protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline PVR at week 25 |
Cambio desde la basal en la resistencia vascular pulmonar (RVP) en la semana 25 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At week 25 |
En la semana 25 |
|
E.5.2 | Secondary end point(s) |
- Change from baseline in 6MWD at week 13 and week 25 - Right heart catheterization assessments including RV pressures, pulmonary artery pressures, wedge pressure, and cardiac output at week 25 - Change from baseline in tricuspid annular plane systolic excursion (TAPSE) by echocardiography at week 5, 13 and 25 - Change from baseline in tricuspid annular systolic velocity (TASV) by echocardiography at week 5, 13 and 25 - Change from baseline of peak velocity of excursion (RV S') by echocardiography at week 5, 13 and 25 - Change from baseline in fractional area change (FAC) by echocardiography at week 5, 13 and 25 - Change from baseline in EmPHasis-10 and PAH-SYMPACT at week 13 and 25 - AEs, SAEs, vital signs, ECGs, safety laboratory measurements - Time to Clinical Worsening - Cmax and Tmax (Day 1 and Week 25) |
- Cambio respecto del basal en la prueba de marcha de 6 minutos (6MWD) a la semana 13 y semana 25. - Evaluación de cateterismo cardíaco derecho incluyendo presión en ventrículo derecho, presión arterial pulmonar, presión de enclavamiento y gasto cardíaco en la semana 25 - Cambio respecto del basal en el desplazamiento sistólico del plano del anillo tricuspídeo (TAPSE) por ecocardiografía a las semanas 5, 13 y 25. - Cambio respecto del basal de la velocidad sistólica del anillo tricuspídeo (TASV) por ecocardiografía en visita semana 5, semana 13 y semana 25 - Cambio respecto del basal de la velocidad máxima de excursión (RV S’) por ecocardiografía en visita semana 5, semana 13 y semana 25. - Cambio respecto del basal del área fraccional (FAC) por ecocardiografía en visita semana 5, semana 13 y semana 25. - Cambio respecto del basal en EmPHasis-10 y PAH-SYMPACT en visita semana 13 y semana 25. - Eventos adversos, eventos adversos graves, signos vitales, electrocardiograma, evaluaciones de laboratorio de seguridad. - Tiempo hasta el empeoramiento clínico. - Concentración máxima y tiempo máximo en Día 1 y semana 25. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At weeks 13 and 25 At week 25 At week 5, 13 and 25 At week 5, 13 and 25 At week 5, 13 and 25 At week 5, 13 and 25 At week 13 and 25 Baseline to Week 29 Baseline to Week 29 Day 1 and week 25 |
En la semana 13 y 25 En la semana 25 En la semana 5, 13 y 25 En la semana 5, 13 y 25 En la semana 5, 13 y 25 En la semana 5, 13 y 25 En la semana 13 y 25 Basal hasta la semana 29 Basal hasta la semana 29 Dia 1 y semana 25 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
United States |
Poland |
Netherlands |
Spain |
Germany |
Russian Federation |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LSLV |
Último paciente, última visita |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |